The purpose of this study is to determine the risk factors associated with inhibitor formation in hemophilia A and to study the mechanism of tolerance in the murine hemophilia A model. Clinical data on 364 individuals with hemophilia and inhibitors, and stored frozen plasma and white cells on 189 of these, identified in the Hemophilia Malignancy Study (HMS), and the hemophilia A murine model are available for study. Inhibitor formation in individuals with hemophilia is a difficult therapeutic challenge, refractory to standard treatment, potentially life-threatening, costly, and a potential complication of new treatment, such as gene therapy. The major hypothesis of this study is that suppression of immunoregulatory cytokines will prevent factor VIII inhibitor formation in the hemophilia A murine model: if successful, a treatment protocol could be developed for individuals identified to be at highest risk for inhibitor formation. Through this approach to the epidemiology and immunology of inhibitor formation, the investigators may improve the health care of individuals with hemophilia. The specific aims include: (1) A case-control study comparing prevalent hemophilia patients with inhibitors identified in the HMS Study with three age-matched controls without inhibitors to determine clinical and laboratory characteristics associated with inhibitor development. (2) a histocompatibility study identifying patterns of HLA Class II antigens by molecular typing in hemophilic subjects identified in HMS, with and without inhibitors, which may be linked to inhibitor formation. (3) An animal tolerance study in the hemophilia A murine model, evaluating blockade of T cell costimulatory pathways by CTLA4-Ig and anti-CD40L mAb, to prevent inhibitor formation. (End of Abstract)